Texas Department of State Health Services
Vectorborne Zoonoses: Break-out Session Epidemiology and Laboratory Capacity Workshop – Oct. 2018 DSHS Zoonosis Control Branch Session Topics Texas Department of State Health Services
• NEDSS case investigation tips • Lyme disease • Rickettsial diseases • Arboviral diseases
ELC 2018 - Vectorborne Diseases 2 Texas Department of State Health Services
Don’t be a Reject! Helpful tips to keep your notification from being rejected
ELC breakout session October 3, 2018 Kamesha Owens, MPH Zoonosis Control Branch Texas Department of State Health Services Objectives
• Rejection Criteria • How to document in NBS (NEDSS) • How to Report
Texas Department of State Health Services
10/3/2018 ELC 2018 - Vectorborne Diseases 4 Rejection Criteria Texas Department of State Health Services
Missing/incorrect information: • Incorrect case status or condition selected • Full Name • Date of Birth • Address • County • Missing laboratory data
10/3/2018 ELC 2018 - Vectorborne Diseases 5 Rejection Criteria continued Texas Department of State Health Services
• Inconsistent information • e.g. Report date is a week before onset date • Case investigation form not received by ZCB within 14 days of notification • ZCB recommends that notification not be created until the case is closed and the investigation form has been submitted
10/3/2018 ELC 2018 - Vectorborne Diseases 6 Rejection Criteria continued Texas Department of State Health Services
• Condition-specific information necessary to report the case is missing: • Travel history for Zika and other non-endemic conditions • Evidence of neurological disease for WNND case • Supporting documentation for Lyme disease case determination
10/3/2018 ELC 2018 - Vectorborne Diseases 7 How to Document in NBS (NEDSS) Do Don’t Add detailed comments in designated Leave us guessing! comments box under case info tab. If you decide not to enter comments, (strongly recommended not required) please make sure information on paper form is legible. Ensure all fields required to be entered Leave important fields blank, are filled in or selected. i.e. symptoms, lab results, date of • Check your dates (Onset date, date report, etc. of report, etc.) to ensure the timeline reflected makes sense and is accurate.(See DEG for details) Check NBS entry against paper form to Leave out Condition-specific make sure the information is the same. information necessary to report a case (i.e. travel dates and history for Zika cases). Enter a comment in ALL positive ELRs Leave positive ELRs comments section for non-cases explaining why the case- blank or not associate relevant patient does not meet case definition or is appropriate labs to case “lost to follow-up” (LTF) unless the ELRs investigations. are associated with an NBS investigation. 10/3/2018 ELC 2018 - Vectorborne Diseases 8 Reporting Zoonoses
• For LHDs: Scan and attach, fax, or send via secure e-mail the completed investigation form with relevant lab reports to your Regional ZC office for review • After review, the Regional ZC staff will forward to ZCB Texas Department of State Health Services Central Office for final review and approval
10/3/2018 ELC 2018 - Vectorborne Diseases 9 Reporting Zoonoses
For ZC Regional Staff: Scan and attach, fax, or send via secure e-mail completed case investigation form with relevant lab reports to Central Office ZCB epidemiologists for
Texas Department of State review and approval Health Services
10/3/2018 ELC 2018 - Vectorborne Diseases 10 Attaching Documents in NEDSS • Not all Conditions allow this • Scan/Save the completed form and laboratory reports as a pdf • Attach the document under the Supplemental Info tab of the case investigation • Scroll down until you see “Attachments” under the “Notes and Attachments” section, then click on the button that is
Texas Department of State labeled “Add Attachment” Health Services
Date Added Added By File Name Description Nothing found to display .
Add Attachment
10/3/2018 ELC 2018 - Vectorborne Diseases 11 Resources
• TDSHS Zoonosis website: http://www.dshs.texas.gov/idcu/ health/zoonosis/ • IDCU: http://www.dshs.texas.gov/idcu/ default.shtm • NBS Data Entry Guide (DEG): https://txnedss.dshs.state.tx.us:8009/ PHINDox/UserResources/ Texas Department of State Health Services • Epi Case Criteria Guidelines (ECCG): https://txnedss.dshs.state.tx.us:8009/ PHINDox/UserResources/
10/3/2018 ELC 2018 - Vectorborne Diseases 12 Texas Department of State Health Services
Lyme Disease Case Classification and Two-Tiered Testing
Bonny Mayes, MA, RYT Epidemiologist Zoonosis Control Branch Department of State Health Services Austin, Texas Lyme Disease Causative Agent: Spirochete bacterium Borrelia burgdorferi sensu stricto in US (5 other Borrelia sp in Europe or Asia) Vectors: Blacklegged tick (deer tick), Ixodes scapularis, and western blacklegged tick, Ixodes pacificus, on Pacific Coast Incubation Period: 3-32 days after exposure (mean 7- 10 days) for EM rash and/or flu-like symptoms Transmission: Transmission generally does not occur until after tick has been attached for at least 36 hours
ELC 2018 - Vectorborne Diseases 14 The Enzootic Cycle of Borrelia burgdorferi
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t. "'J Q . Spirochaete
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Rcplctcfc• ~ drop~ to ground Adult feeds on ti nd lily) egg$ third hose
Erythcmil m,gr.>n~
www.nature.com/nrmicro/journal/v10/n2/fig_ tab/nrmicro2714 _ F1.html 15 ELC 2018 - Vectorborne Diseases Lyme Disease Clinical Presentation
A systemic, tickborne disease with protean manifestations, including dermatologic, rheumatologic, neurologic, and cardiac abnormalities. The best clinical marker for the disease is the initial skin lesion, erythema migrans (EM). For most patients, the expanding EM lesion is accompanied by other acute symptoms, particularly fatigue, fever, headache, mildly stiff neck, arthralgia, or myalgia.
www.cdc.gov/lyme/signs_symptoms/index.html 16 ELC 2018 - Vectorborne Diseases Erythema Migrans (EM) Rash www.cdc.gov/lyme/signs_symptoms/index.html • Occurs in approximately 70 to 80 percent of infected persons • Begins at the site of a tick bite after a delay of 3 to 30 days (average is about 7 days) • Expands gradually over a period of days reaching up to 12 inches or more (30 cm) in diameter • May feel warm to the touch but is rarely itchy or painful • Sometimes clears as it enlarges, resulting in a target or “bull's -eye” appearance • May appear on any area of the body • Annular erythematous lesions occurring within several hours of a tick bite represent hypersensitivity reactions and do not qualify as EM!
Lyme Disease rashes and Look- alikes: www.cdc.gov/lyme/signs_symptoms/rashes.html
“classic” Lyme disease rash Itchy rash due to insect bites 17 ELC 2018 - Vectorborne Diseases Lyme Disease 2018 Case Definition/Case Classification
Confirmed: A case with physician -diagnosed EM ≥ 5 cm in size with an exposure in a high-incidence state or country*, OR a case of physician -diagnosed EM ≥ 5 cm in size with laboratory confirmation with an exposure in a low-incidence state or country*, OR a case with at least one late manifestation that has laboratory confirmation.
*Exposure is defined as having been (≤ 30 days before onset of EM) in wooded, brushy, or grassy areas (i.e., potential tick habitats). An exposure in a high-incidence state is defined as exposure in a state with an average Lyme disease incidence of at least 10 confirmed cases/100,000 persons for the previous three reporting years. A low-incidence state is defined as a state with disease incidence of <10 confirmed cases/100,000 persons for the previous three reporting years. www.cdc.gov/lyme/stats/tables.html
Texas is considered a low - incidence state for Lyme disease! ELC 2018 - Vectorborne Diseases 18 Lyme Disease High Incidence Areas • Most commonly reported vector-borne illness in the United States • Does not occur nationwide and is concentrated heavily in the northeast and upper Midwest
High Incidence States: Connecticut, Delaware, Maine, Maryland, Massachusetts, Minnesota, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Vermont, Virginia, www.cdc.gov/lyme/stats/index.html Wisconsin Outside of the US Lyme disease is common in some forested areas in Europe. Countries with highest reported incidence include Germany, Austria, Slovenia, and Sweden.* *Infectious Disease Clinics of North America, Vol. 22/Ed. 2, Fish AE, Pride YB, Pinto DS, Lyme carditis, 275-288 ELC 2018 - Vectorborne Diseases 19 Lyme Disease 2018 Case Definition/Case Classification
Confirmed: A case with physician -diagnosed EM ≥ 5 cm in size with an exposure in a high -incidence state or country, OR a case of physician -diagnosed EM ≥ 5 cm in size with laboratory confirmation with an exposure in a low -incidence state or country, OR a case with at least one late manifestation* that has laboratory confirmation.
First-Degree AV Block
Second-Degree AV Block (2:1)
ELC 2018 - Vectorborne Diseases 20 Lyme Disease 2018 Case Definition/Case Classification *For purposes of surveillance, late manifestations include any of the following when an alternate explanation is not found: wwwn.cdc.gov/nndss/conditions/lyme-disease/case-definition/2017/
• Musculoskeletal system: recurrent, brief attacks (weeks or months) of objective joint swelling in one or a few joints, sometimes followed by chronic arthritis in one or a few joints. • NOT: chronic progressive arthritis not preceded by brief attacks; chronic symmetrical polyarthritis or arthralgia, myalgia, or fibromyalgia syndromes alone
• Nervous system: any of the following, alone or in combination: lymphocytic meningitis; cranial neuritis, particularly facial palsy (can be bilateral); radiculoneuropathy; or, rarely, encephalomyelitis. • NOT: headache, fatigue, paresthesia, or mildly stiff neck alone
• Cardiovascular system: acute onset of high -grade (2nd or 3rd- degree) atrioventricular conduction defects that resolve in days to weeks and are sometimes associated with myocarditis. • NOT: palpitations, bradycardia, bundle branch block, or myocarditis alone ELC 2018 - Vectorborne Diseases 21 Lyme Disease 2018 Case Definition/Case Classification
Probable: Any other clinically compatible* case of physician- diagnosed Lyme disease that has laboratory confirmation *fever, chills, headache, fatigue, muscle & joint aches, swollen lymph nodes, EM rash
Suspect: A case of EM with no known exposure and no laboratory evidence of infection, OR a case with laboratory evidence of infection, but no clinical information available
Note: Lyme disease reports will not be considered cases if the medical provider specifically states this is not a case of Lyme disease, or the only symptom listed is “tick bite” or “insect bite”
ELC 2018 - Vectorborne Diseases 22 Lyme Disease Laboratory Confirmation Tests Positive culture for Borrelia burgdorferi OR IgG immunoblot seropositivity using established criteria* OR IgM immunoblot seropositivity using established criteria* with positive/equivocal EIA or IFA test AND specimen collected ≤30 days after symptom onset
Notes: • *CDC Immunoblot interpretation criteria • While a single IgG WB is adequate for surveillance purposes, a two - tier test is still recommended for patient diagnosis.
ELC 2018 - Vectorborne Diseases 23 Lyme Disease Immunoblot (Western Blot) CDC Interpretation Criteria
IgM immunoblot ▪ Considered positive if 2 of the following 3 bands are present: 24 kDa (*OspC), 39 kDa (BmpA), and 41 kDa (Fla)
IgG immunoblot OipB _ _ _ ▪ Considered positive if 5 of the OspA _ following 10 bands are present: 18 kDa, 24 kDa (*OspC), 28 kDa, 30 OspC ► ■ kDa, 39 kDa (BmpA), 41 kDa (Fla), 45 22 -11 kDa, 58 kDa, 66 kDa, and 93 kDa wwwn.cdc.gov/nndss/conditions/lyme -disease/case -definition/2017/ *Depending upon the assay, OspC could be indicated by a band of 21, 22, 23, 24 or 25 kDA
ELC 2018 - Vectorborne Diseases 24 Two-Tiered Testing for Lyme Disease
First Test Second Test
TEXAS Enzyme Health and Human Services Immunoassay Signs or lgM and lgG Texas Department of State symptoms Health S•rvices (EIA) Rositive Western Blot or. ~ 30 days Eguivocal IResl!llt Signs or lgG Western Blot lmmunofluorescence symptoms ONLY Assay > 30 days (IFA) Negative Result
Consider alternative diagnosis
If patient w ith signs/ symptoms consistent with Lyme disease for $ 30 days, consider obtaining a convalescent serum
Nationi\l Center for Emerging and Zoonotic lnfectiouc; Oi~eac;es
Division ofVec tor Borne Diseases I Bacterial Diseases Bra nch I
https://www.cdc.gov/lyme/diagnosistesting/labtest/twostep/index.html ELC 2018 - Vectorborne Diseases 25 Lyme Disease ELISA or EIA (Screen) • False-negative results common if tested too early ▪ Only 50% sensitivity if test taken within first two weeks of infection ▪ Patients with EM typically seronegative • Sensitivity of screen is very good AFTER the EM stage of illness ▪ Antibody levels may remain elevated for months to years after treatment! • False positive results are an issue also - some possible causes of false-positive screening tests include: ▪ Tick-borne relapsing fever ▪ Syphilis (Treponema pallidum) ▪ Periodontal disease (Treponema denticola) ▪ Systemic lupus erythematosus ▪ Acute Epstein-Barr virus infection ▪ Helicobacter pylori ▪ Subacute bacterial endocarditis ▪ Rheumatoid arthritis ELC 2018 - Vectorborne Diseases 26 Lyme Disease IgM Immunoblot Issues
• Omitting the screen and using immunoblot only decreases specificity of serological testing! ▪ Immunoblot will NOT be done if screen is negative ▪ With NO screen, more immunoblots will be run Monomer – some will be false positives lgD, lgE, lgG ▪ Erroneous scoring of a faint band is a common
reason for false-positive readings Dimer lgA ▪ IgM results more affected by this problem: ➢ IgM Abs are more non-specifically “sticky” than IgG Abs ~ 11tamer lgM ➢ Only 2 of 3 bands are required for an IgM to be reported as positive (as opposed to 5 of 10 for IgG) ➢ “A single erroneously scored faint band will affect IgM results more readily than it will affect IgG results.”
Johnson, B.J. "Chapter 4: Laboratory diagnostic testing for Borrelia burgdorferi infection" in Lyme disease: An Evidence-based Approach, J.J. Halperin, Ed. (CAB International, 2011). Complete Article Reproduced with Permission ELC 2018 - Vectorborne Diseases 27 Examples of Lyme Screens and Immunoblots Lyme Screens (EIA/ELISA/IFA): ➢ Lyme disease (Borrelia burgdorferi) Antibody Screen: 1.22 - (Final) Enzyme-Linked ➢ Borrelia burgdorferi Ab.IgG+IgM: lmmunosorbent Assay 1.47 index
wash ➢ Borrelia burgdorferi Ab.IgM: 01. AnUger.,. coa1edwell - -o2. Bloc~ ;;:~~ 5. Add 0.94 index ~~spec_ific 4. Add enzyme- substrate b1nd1ng sil~s eonjugaled and measure ➢ BORRELIA BURGDORFERI AB: f :If'" anUt>Ody coo.- wash f
Positive 3. fv:Jd patient's 80 serum (antibody) Lyme IFA Screen Indirect Immunoblots (Western Blots) immunofluorescence assay ➢ Borrelia burgdorferi Ab.IgM band pattern: Positive ➢ B BURGDOR IGG SER QL IB: Positive ➢ Borrelia burgdorferi antibody band pattern: Lyme IgG Western Blot - bands 30, 39, 41, 45, and 58 present positive ➢ Borrelia burgdorferi 28kD Ab.IgG: Present or Absent (Labcorp - there will be a separate ELR for
all 10 bands) ELC 2018 - Vectorborne Diseases 28 Lyme Disease Laboratory Tests That Are NOT Recommended Some laboratories offer Lyme disease testing using assays for which the accuracy and clinical usefulness have NOT been adequately established.
Examples of unvalidated tests include: • Capture assays for antigens in urine • Culture, immunofluorescence staining, or cell sorting of cell wall - deficient or cystic forms of B. burgdorferi • Lymphocyte transformation tests • Quantitative CD57 lymphocyte assays • “Reverse Western blots” • In- house criteria for interpretation of immunoblots • Measurements of antibodies in joint fluid (synovial fluid) • IgM immunoblot tests without a previous ELISA/EIA/IFA • Lyme CSF Ab tests www.cdc.gov/lyme/diagnosistesting/labtest/otherlab/index.html www.medscape.com/viewarticle/764501?src=par_cdc_stm_mscpedt&faf=1 PCR testing has limitations…DNA testing does not distinguish between living and dead organisms, and laboratory contamination with amplified DNA poses a risk for false-positive results…Is PCR useful for the diagnosis of Lyme disease? In general, the answer is no. ELC 2018 - Vectorborne Diseases 29 T A CASE Texas resident make a note in lab report in NBS and Transfer Ownership to Out of Texas NBS 2018 Lyme Disease (LD) ,Classification Hea lthcare provider (HCP) NOT A CAS E Algorithm specifically states make a not e in lab report in NBS this is NOT a case Page 1 {Rev. 4-18) of Lyme disease
Erythema migrans EM~ 5 cm as Clin ical evidence of LD late (EM)~ 5 cm as observed by HCP manifestation (Lyme See Page 2 for Probable observed by HCP w ith exposure arthrit is, Be ll's palsy, etc.) LD determination with exposure in outside of high where an al t ernate "high incidence incidence area explanation is not found state or country
Was an Was the Pos itive culture EIA/ELISA or IFA EIA/EUSA or IFA for Borre/ia NOT A CASE screen equivocal Confirmed LID burgdorferi or posit ive?
Posit ive lgG Positive lgG lmmunoblot Confirmed LD lmmunoblot O R NOT A CASE Posit ive lgM lmmunoblot coll ected S30 days after onset "see http:ljwww.cdc.gov/lyme/stats/index.html for Lyme incidence data lmmunoblot = Western Blot (per CDC criteria) EIA/ELISA = enzyme immunoassay/enzyme Confirmed LD linked immunosorbent assay TEXAS Texas Department of State IFA = immunofluorescence assay ELC 2018 - VectorborneConfirmed Diseases LD Health and Human 30 Services Health Services Continued from page 1) TEXAS Health and Human Texas Department of State Services Hea lth Services Other LO-compatible clinical signs and symptoms (fatigue, fever, headache, mildly st iff NOT A CAS E neck, arthralgia, or mya lgia)
Was an Was the Posit ive culture for EIA/ELISA or IFA EIA/ELISA or IFA NOT A CAS E Borrelia screen equ ivocal burgdorferi or posit ive?
Posit ive lgG Posit ive lgG lmmunoblot Probable LO OR llmmunoblot NOT A CASE Posit ive lgM lmmunoblot collected S30 days after onset
Probable LO Probable LO
2018 Lyme Disease (LD}
" see http:ljwww.cdc.gov/lyme/stats/index.html for Lyme incidence data ,case ,Classification lmmunoblot = Western Blot (per CDC cr iteria) EIA/HISA = enzyme immunoass ay/ enzyme-linked immunosorbent assay IFA = immunofluorescence assay Algorithm
ELC 2018 - Vectorborne Diseases 31 Page 2 (Rev. 4-18) Lyme Disease Case Investigation
• IgM positive blot is only relevant if screen performed and was equivocal or positive • Onset date important! ▪ IgM positive blot only relevant if specimen collected ≤30 days after symptom onset • Make sure all lab reports are in NEDSS • Physician does not have to definitively diagnose patient with Lyme disease (“will not be considered cases if the medical provider specifically states this is not a case of Lyme disease”) • Inquire about travel history! • Consider “alternate explanation” ▪ Rheumatoid arthritis, lupus, etc. • Make sure all required fields are completed in NEDSS (refer to Data Entry Guidelines – Quick Reference section for patient demographics/lab report)
ELC 2018 - Vectorborne Diseases 32 Useful Resources
• DePietropaolo DL, Powers JH, Gill JM. Diagnosis of Lyme Disease. Am Fam Physician. 2006 Mar 1;73(5):776. ➢ clinical recommendations, how to determine pre-test probability, interpretation of serologic testing • Lantos PM, et al. Poor Positive Predictive Value of Lyme Disease Serologic Testing in an Area of Low Disease Incidence. Clin Infect Dis. 2015 Nov 1;61(9):1374-80. doi: 10.1093/cid/civ584. Epub 2015 Jul 20. ➢ study on positive predictive value of two-tiered testing • www.cdc.gov/lyme/ ➢ signs and symptoms, treatment, diagnosis and testing, data and statistics, transmission, post-treatment Lyme disease syndrome, info for healthcare providers, educational materials, tick bite/removal/testing info • www.dshs.state.tx.us/idcu/disease/lyme/ ➢ overview, data, resources
ELC 2018 - Vectorborne Diseases 33 Scenario 1
• Patient • 39 yo male that resides in Central Texas; denies outdoor activity, other than sitting in back yard with dog at night (backyard faces woods); did travel to Indiana for a wedding 3 weeks prior but spent no time outdoors • Clinical Information • Fever/sweats/chills, arthralgias, myalgias, neck pain, fatigue, adenopathy, confusion, Bell’s palsy, radiculoneuropathy • Lab results • Lyme EIA screen positive/IgM WB positive • WNV IgM positive at CPL (6.85 acute, 1.95 conval) • Dengue IgM negative • Diagnosis • Subacute disseminated Lyme disease
ELC 2018 - Vectorborne Diseases 34 Scenario 1 (cont.)
• Requested follow up testing at CDC
• PRNT at CDC: • Negative for DEN, SLE, WNV, ZIKV
• Tick-borne Relapsing Fever • TBRF EIA & WB Positive!
• Classified as “Not a Case” for Lyme Disease
ELC 2018 - Vectorborne Diseases 35 Scenario 2
• Patient • 12 yo male that resides in South Texas – no recent travel outside of county of residence • Clinical Information • Arthralgias, fatigue, muscle weakness, myalgia, shortness of breath • Symptom onset gradual, followed tick bite months prior • Lab results • Lyme EIA screen equivocal/IgM WB positive (IgG negative) • DOC in March (onset in prior year) • Diagnosis • Early disseminated Lyme disease (med records state “previously negative for Lyme disease and is IgG and IgM positive and confirmed by reflex testing”)
ELC 2018 - Vectorborne Diseases 36 Scenario 2
• Classified as Not a Case
• Lab results • Lyme EIA screen equivocal/IgM WB positive (IgG negative) • DOC in March (onset in prior year) • IgM blot is not relevant if onset is more than 30 days prior to DOC!
ELC 2018 - Vectorborne Diseases 37 Scenario 3
• Patient • 45 yo female that resides in East Texas • No travel outside of Texas • Frequently walks in park
• Clinical information • Fever, headache, arthralgias, fatigue, myalgias
• Lab results • IgG WB positive • DOC in July (onset mid-February)
• Diagnosis • Not stated in med records, but patient was treated with doxycycline for 2 weeks
ELC 2018 - Vectorborne Diseases 38 Scenario 3
• Classified as Probable Lyme Disease case • No EM or late manifestation
• Lab results • IgG WB positive
• Confirmatory: IgG immunoblot seropositivity using established criteria
• While a single IgG WB is adequate for surveillance purposes, a two-tier test is still recommended for patient diagnosis
ELC 2018 - Vectorborne Diseases 39 Texas Department of State Health Services
Rickettsial Disease Diagnostics and Epidemiology
Bonny Mayes, MA, RYT Zoonosis Control Branch Department of State Health Services Austin, Texas Rickettsial Infections Spotted Fever & Typhus Groups
Typhus Group ➢ Rickettsia prowazekii (louse-borne, epidemic, sylvatic typhus) ➢ R. typhi (flea-borne, endemic, murine typhus)
Spotted Fever Group (tick- borne) ➢ R. aeschlimannii (Rickettsiosis) ➢ R. africae (African tick-bite fever) ➢ R. australis (Queensland tick typhus) ➢ R. conorii (Mediterranean spotted fever, Boutonneuse fever) ➢ R. heilongjiangensis (Far Eastern spotted fever) ➢ R. Helvetica (Aneruptive fever) ➢ R. honei (Flinders Island spotted fever, Thai tick typhus) ➢ R. japonica (Japanese spotted fever) ➢ R. marmionii subspecies (Australian spotted fever) http://www.microbeworld.org/inde x.php?option = com_jlibrary&view = ➢ R. massiliae (Mediterranean spotted fever-like disease) article&id = 3343 ➢ R. parkeri (Maculatum infection) ➢ R. rickettsii (Rocky Mountain Spotted Fever) ➢ R. sibirica (North Asian tick typhus, Siberian tick typhus) ➢ R. sibirica mongolotimonae (Lymphangitis-associated rickettsiosis) ➢ R. slovaca (Tickborne lymphadenopathy) ➢ Rickettsia species 364D http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious -diseases- related -to -travel/rickettsial- spotted -typhus - fevers -related- infections- anaplasmosis -ehrlichiosis http://www.cdc.gov/otherspottedfever/ ELC 2018 - Vectorborne Diseases 41 Flea-borne Typhus
• Etiologic Agent: ➢ bacterium Rickettsia typhi (and possibly R. felis) • Vectors: ➢ primarily rat fleas (Xenopsylla cheopis) and cat fleas (Ctenocephalides felis) • Reservoirs: ➢ rats, opossums, domestic cats, and other small mammals • Modes of transmission: ➢ transmission to humans can occur when flea feces*, containing the bacteria, are scratched into the bite site or other abrasion in the skin, or are rubbed into the conjunctiva ➢ another possible mode of transmission is inhalation of dried rat or cat flea feces*
*Infection by R. felis has been attributed to flea saliva rather than feces http://www.ehtjournal.net/index.php/ehtj/article/view/7168/9204#CIT0013 ELC 2018 - Vectorborne Diseases 42 Flea-borne Typhus History
• Also known as murine or endemic typhus • Worldwide distribution • First identified in the United States in 1913 • Over 5,000 cases were reported annually through the mid- 1940’s mainly in SE states and California • 1945 US Public Health Service initiated campaign to control rats and their fleas – by late 1980’s, case counts reduced to less than 100 cases/yr • Most states discontinued reporting flea-borne typhus after the drastic reduction of cases • Not nationally reportable, so reliable case counts are not known • Still reportable in some states, including Texas, California and Hawaii, where the majority of cases are thought to occur
ELC 2018 - Vectorborne Diseases 43 Flea-borne Typhus Disease in Humans
• Symptoms occur from 6 to 14 days after exposure • Most common symptoms include: ➢ Fever ➢ Headache ➢ Malaise ➢ Anorexia ➢ Myalgia ➢ Nausea and/or vomiting ➢ Rash – occurs in ~50% of those infected ▪ Generally starts on trunk and spreads to the arms and legs but usually does not occur on the face, palms or soles ➢ Thrombocytopenia* *reported in 16% of cases in Texas, 2003 -2013 ** reported in 27% of cases in Texas, 2003 -2013 ➢ Elevated liver enzymes** • Typhus-associated deaths are rare but may occur in 5% of those infected
ELC 2018 - Vectorborne Diseases 44 Flea-borne Typhus Epidemiology in Texas
• Flea-borne typhus has been included in the Annual Summary of Notifiable Diseases in Texas since 1946 Flea-borne Typhus • From 1946 to 2014, there 2008-2014 were 6,729 cases reported (mean=97.5); highest number of cases reported in 1946 (n=1147) and lowest in 1994 (n=9) • Typhus cases occur year round, but majority of cases Cases/ County occur from May to July 1 - 7 8 - 21 22 - 48 • Most cases occur in the 49 - 197 southern portion of the 198 - 490 state, from Nueces County southward to the Rio Grande Valley
ELC 2018 - Vectorborne Diseases 45 Reported Typhus Cases in Texas by Year, 2004-2017
0 2 2 5 2 2 7 2010 2 l 2012 JOB 201 2015 2016 2017
ELC 2018 - Vectorborne Diseases 46 Hot Spot Analysis of Typhus Cases in Texas, 2013
• ~,:-t.usCil$C 10011nlt-'lf!'l'~!J(l'lil<"..r1(1 - COICI S:pc,-1 - OQ't. COl'lnotni:t - COia S Hot Spot Analysis of Typhus Cases in Texas, 2017" •p,~IO&al dm, • 1)pntl1:Case t00klll1 He,agonalGnd - COi~ S«>t •99'4 CClllid!flct - C ELC 2018 - Vectorborne Diseases 47 Tick-borne Spotted Fever Group Rickettsia (SFGR) • Etiologic Agents (in the U.S.): ➢ Rickettsia sp. Bacteria ▪ Rickettsia rickettsii (Rocky Mountain Spotted Fever) ▪ Rickettsia parkeri (Maculatum infection) ▪ Rickettsia species 364D (Eschar-associated illness) ▪ Rickettsia amblyommii?? (detected in many ticks; pathogenicity has not been determined) • Vectors: ➢ Rickettsia rickettsii - mainly: ▪ The American dog tick (Dermacentor variabilis), Rocky Mountain dog tick (Dermacentor andersoni), brown dog tick (Rhipicephalus sanguineus), cayenne tick (Amblyomma cajennense) ➢ Rickettsia parkeri: ▪ Gulf Coast tick (Amblyomma maculatum) ➢ Rickettsia species 364D ▪ Pacific Coast tick (Dermacentor occidentalis) • Reservoirs: ➢ ticks; dogs and rodents • Modes of transmission: ➢ transmitted to a vertebrate host via the bite of an infected tick ➢ generally, the tick must be attached and feeding for about 24 hours before the bacteria can be transmitted to the host ELC 2018 - Vectorborne Diseases 48 SFGR History • Rocky Mountain spotted fever (RMSF), the protypic disease of the spotted fever group, has been a reportable disease in the US since the 1920’s • This disease was first described in the Rocky Mountain region of the US, but has been reported throughout most of the contiguous US • The majority of cases (>60%) are reported from only five states (North Carolina, Oklahoma, Arkansas, Tennessee and Missouri) 2500 "'~ m ..u 2000 :,"' a: ... 1500 0 '- i 1000 www.cdc.gov/rmsf/stats/ E ~ 500 • As of 2010, RMSF has been included in a broader category called Spotted Fever Group Rickettsiosis (SFGR) - many of the cases being reported as RMSF were not actually identified as being specifically Rickettsia rickettsii ELC 2018 - Vectorborne Diseases 49 SFGR Disease in Humans • Disease onset averages one week following the bite of an infected tick (for RMSF, first symptoms typically begin 2- 14 days after tick bite) • Most common symptoms include: ➢ Fever ➢ Headache ➢ Myalgia ➢ Anemia ➢ Myalgia ➢ Nausea and/or vomiting ➢ Rash – occurs in >80% of those infected with RMSF ▪ generally starts on ankles and wrist and spreads to the torso; often present on the palms and soles ➢ Thrombocytopenia ➢ Elevated liver enzymes • RMSF can be fatal in as many as 20% of untreated cases ELC 2018 - Vectorborne Diseases 50 Spotted Fever Epidemiology in Texas • Rocky Mountain Spotted Fever/Spotted Fever Spotted Fever Group Group Rickettsiosis has Rickettsiosis Cases been included in the 2008-2014 Annual Summary of Notifiable Diseases in Texas since 1951 • From 1951 to 2014, there were 1,353 cases reported Cases I County (mean=21); highest 1 • 2 3 - 5 6 - 11 number of cases reported 12 • 26 in 1983 (n=108) and 27 • 118 lowest in 1958, 1962, 1965 and 2001 (n=0) ELC 2018 - Vectorborne Diseases 51 Flea-borne Typhus and SFGR in Texas, 2008-2014 ■ Sum of SFGR ■ Sum of Typhus 2008 2009 2010 2011 2012 2013 2014 Spotted Fever Group Rickettsiosis Cases Flea-borne Typhus 2008-2014 2008-2014 1 - 7 8 - 21 22 - 48 49 - 197 198 - 490 52 Flea-borne Typhus Epi Case Criteria 2018 Case Definition/Case Classification Flea-borne typhus is a rickettsial disease whose course resembles that of louse-borne typhus, but is generally milder. The onset is variable, often sudden and marked by headache, chills, fatigue, fever and general pains. A macular rash may appear on the 5th or 6th day, initially on the upper trunk, followed by spread to the entire body, but usually not to the face, palms or soles. Absence of louse infestation, geographic and seasonal distribution, and sporadic occurrence of the disease help to differentiate it from louse-borne typhus. ELC 2018 - Vectorborne Diseases 53 Flea-borne Typhus Epi Case Criteria 2018 Case Definition/Case Classification (cont.) Clinical evidence: Any reported acute onset of fever and one or more of the following: headache, myalgia, anorexia, rash, nausea/vomiting, thrombocytopenia, or any hepatic transaminase elevation. Confirmed: Clinically compatible case that is laboratory confirmed Probable: Clinically compatible case with supportive laboratory results: • IFA serologic titer of ≥1:128, OR • A single CF of >16, OR • Other supportive serology (single titer ≥1:128 by an LA, IHA, or MA test) Note: Because serologies for rickettsial diseases can be cross- reactive, specimens should be tested against a panel* of Rickettsia antigens, including, at a minimum, R. rickettsia and R. typhi, to differentiate between SFGR and non-SFGR Rickettsia spp. In addition, according to CDC, Rickettsial IgM tests lack specificity (resulting in false positives); thus, IgG titers are considered to be much more reliable. * Specimens can be forwarded to the DSHS Serology lab for Rickettsial panel testing. ELC 2018 - Vectorborne Diseases 54 Flea-borne Typhus Epi Case Criteria 2018 Laboratory Confirmation Tests Serological evidence of an elevation (four-fold change) in immunoglobulin G (IgG)-specific antibody titer reactive with R. typhi or R. felis by IFA, complement fixation (CF), latex agglutination (LA), microagglutination (MA), or indirect hemagglutination antibody (IHA) test in acute – and convalescent – phase specimens ideally taken at least 3 weeks apart, OR Positive PCR assay to R. typhi or R. felis, OR Demonstration of positive R. typhi or R. felis IF of skin lesion (biopsy) or organ tissue (autopsy), OR Isolation of R. typhi or R. felis from clinical specimen ELC 2018 - Vectorborne Diseases 55 SFGR Epi Case Criteria 2018 Case Definition/Case Classification Spotted fever group rickettsioses (SFGR) are a group of tick- borne infections caused by some members of the genus Rickettsia. The most well -known SFGR is Rocky Mountain spotted fever (RMSF), an illness caused by Rickettsia rickettsii. Disease onset for RMSF averages one week following a tick bite. Illness is characterized by acute onset of fever and can be accompanied by headache, malaise, myalgia, nausea/vomiting, or neurologic signs; a macular or maculopapular rash may appear 4 -7 days following onset in many (~80%) patients, often present on the palms and soles. RMSF can be fatal in as many as 20% of untreated cases, and severe fulminant disease can occur. In addition to RMSF, human illness associated with other spotted fever group Rickettsia species, including infection with Rickettsia parkeri, has also been reported. In these patients, clinical presentation appears similar to, but can be milder than, RMSF; the presence of an eschar at the site of tick attachment has been reported for some other SFGR. ELC 2018 - Vectorborne Diseases 56 SFGR Epi Case Criteria 2018 Case Definition/Case Classification (cont.) Clinical evidence: Any reported acute onset of fever and one or more of the following: rash, eschar, headache, myalgia, anemia, thrombocytopenia, or any hepatic transaminase elevation. Confirmed: Clinically compatible case (meets clinical evidence criteria) that is laboratory confirmed Probable: Clinically compatible case (meets clinical evidence criteria) with serological evidence of elevated IgG or IgM antibody reactive with R. rickettsii or other spotted fever group antigen* by IFA (serologic titer of ≥1:128) Note: Because serologies for rickettsial diseases can be cross- reactive, specimens should be tested against a panel* of Rickettsia antigens, including, at a minimum, R. rickettsia and R. typhi, to differentiate between SFG and non-SFG Rickettsia spp. In addition, according to CDC, Rickettsial IgM tests lack specificity (resulting in false positives); thus, IgG titers are considered to be much more reliable. * Specimens can be forwarded to the DSHS Serology lab for Rickettsial panel testing. ELC 2018 - Vectorborne Diseases 57 SFGR Epi Case Criteria 2018 Laboratory Confirmation Tests Serological evidence of an elevation (four -fold change) in immunoglobulin G (IgG)- specific antibody titer reactive with Rickettsia rickettsii or other spotted fever group antigen* between paired serum specimens (one taken in the first week of illness and a second 2 -4 weeks later), as measured by a standardized indirect immunofluorescence assay (IFA), OR Detection of R. rickettsii or other spotted fever group DNA* in a clinical specimen by polymerase chain reaction (PCR) assay, OR Demonstration of spotted fever group antigen* in a biopsy/autopsy specimen by IHC, OR Isolation of R. rickettsii or other spotted fever group rickettsia* from a clinical specimen in cell culture * Note: Spotted fever group species included are: R. aeschlimannii, R. africae, R. australis, R. conorii, R. heilongjiangensis, R. helvetica, R. honei, R. japonica, R. marmionii, R. massiliae, R. parkeri, R. rickettsii, R. sibirica, R. sibirica mongolotimonae, R. slovaca. Spotted fever group species excluded from this condition are: R. felis and R. akari ELC 2018 - Vectorborne Diseases 58 Typhus & SFGR - Clinical Evidence Flea-borne Typhus Spotted Fever Group Rickettsiosis Must have Fever Must have Fever Headache Headache Myalgia Myalgia Anemia Anorexia (*reported in 52% of cases in Texas, 2003-2013) Rash, if present, typically starts on Rash occurs in ~80% of patients with upper trunk and spreads, but generally RMSF; typically begins on ankles and not to palms/soles (*reported in <50% wrists and spreads to trunk – may be of cases in Texas, 2003-2013) on palms/soles Nausea/vomiting (*reported in 51% of Nausea/vomiting cases in Texas, 2003-2013) Thrombocytopenia (*reported in 16% Thrombocytopenia of cases in Texas, 2003-2013) Elevated liver enzymes (*reported in Elevated liver enzymes 27% of cases in Texas, 2003-2013) ELC 2018 - Vectorborne Diseases 59 Serologic Testing for Rickettsial Diseases • IFA is considered the gold standard of serologic testing for Rickettsial diseases (94-100% sensitive after 14 days – may lack titers in first 7 days of illness) • HOWEVER, “serological testing is limited by antibody cross-reactivity with RMSF and typhus antigens, leading to false positives by both ELISA and IFA” which can contribute to misdiagnosis and misreporting of both diseases • IgM titers are not reliable (CDC: “We do not recommend IgM testing for Rickettsial diseases, especially in the absence of IgG testing, as false positives and false negatives are common.”) • If cost restrictions limit testing, IgG is preferred over IgM! • Physicians need to collect both acute and convalescent serum specimens and order IFA tests • Should test for both (order Rickettsial panel) ELC 2018 - Vectorborne Diseases 60 2014 Probable Typhus Cases - Titers Onset, Date R. typhi R. typhi R. rickettsia R. rickettsia Blood Collected IgM IgG IgM IgG 12/8, 12/15 1:512 1:256 1:512 <1:64 3/25, 4/1 1:128 1:64 1:128 <1:64 1/22, 2/3 1:512 1:512 1:64 1:128 4/11, 4/22 1:128 1:512 1:128 1:128 4/29, 5/2 1:128 1:128 1:64 1:128 12/31, 1/7 1:512 1:256 1:256 1:64 Of the first 45 case investigation forms reviewed, ~25% had positive RMSF titers (and not all had RMSF testing done!) ELC 2018 - Vectorborne Diseases 61 Laboratory Criteria Flea -borne typhus Spotted Fever Group Rickettsiosis Fourfold or greater increase Fourfold or greater increase in IgG Ab in IgG Ab titer in acute and titer in acute and convalescent sera* convalescent sera* (C) (C) IFA* – IgM or IgG Titer of IFA* – IgM or IgG Titer of ≥1:128 ≥1:128 (P) (P) ELISA (EIA) only good for screening purposes – values do not reflect accurate quantification of Ab titers PCR can detect Rickettsia sp. PCR** on punch skin biopsy, swab of and differentiate from R. rash, serum or blood is best test for rickettsii (CDC) RMSF! (CDC) Immunohistochemistry or Immunohistochemistry or culture culture (CDC) (CDC) * A single specimen cannot be used to differentiate between SFGR and flea- borne typhus with confidence ** Must collect during acute phase of illness no more than two days after doxycycline treatment begins ELC 2018 - Vectorborne Diseases 62 Rickettsial Disease Case Investigation Example • Patient with fever/chills, headache, anorexia, photophobia, malaise, myalgia, thrombocytopenia, elevated liver function tests, rash (spread from arms/legs to trunk) • Doctor orders RMSF IgG and IgM ➢IgG 1:128 ➢IgM 1:256 • No convalescent testing • No known tick or flea exposure, no exposure to wild animals, dogs are present at residence • Classified as probable SFGR ELC 2018 - Vectorborne Diseases 63 Rickettsial Disease Case Investigation Example (cont.) • No typhus testing done • ZCB requested that the serum be forwarded from commercial lab to DSHS for Rickettsial panel testing • Results: ➢R. rickettsii IgG 1:128 ➢R. typhi IgG 1:1024 • Changed condition to probable flea-borne typhus! ELC 2018 - Vectorborne Diseases 64 How would you classify this case? Onset, Date R. typhi R. typhi R. rickettsia R. rickettsia Blood Collected IgM IgG IgM IgG 1/8, 1/16 1:256 1:128 1:256 1:128 • Patient has fever, headache, nausea/ vomiting, malaise, thrombocytopenia • Patient does not report exposure to fleas or ticks • Patient does not have rash • Patient from area with both typhus & spotted fever occur • Patient did not travel • Physician unable to get convalescent sample for testing ELC 2018 - Vectorborne Diseases 65 “Rickettsia, unspecified” Epi Case Criteria 2018 Case Definition/Case Classification Flea-borne typhus and spotted fever group rickettsioses (SFGR) are a group of vector-borne infections caused by some members of the genus Rickettsia. These infections can be difficult to differentiate clinically and serologically (due to antibody cross-reactivity). Illness is characterized by acute onset of fever that may be accompanied by: headache, malaise, myalgia, nausea and/or vomiting, anorexia, and rash. Clinical evidence: Acute onset of fever and one or more of the following: rash, headache, nausea/vomiting, anorexia, myalgia, anemia, thrombocytopenia, or any hepatic transaminase elevation. ELC 2018 - Vectorborne Diseases 66 “Rickettsia, unspecified” Epi Case Criteria 2018 Case Definition/Case Classification (cont.) Probable: Clinically compatible case (meets clinical evidence criteria) with serological evidence of elevated IgG or IgM antibody reactive with spotted fever AND typhus group antigens by IFA (serologic titers of ≥1:128) that cannot be classified as either flea-borne typhus or SFGR. Note: For “Rickettsia, unspecified,” an undetermined case can only be classified as probable. This occurs when a case has compatible clinical criteria with laboratory evidence to support infection, but spotted fever and typhus fever group titers are equal. ELC 2018 - Vectorborne Diseases 67 er OTA CASE Flea-bor ,e Typhus least one of, he fo li o ing: Algorit hm rash,. eadache, nausea/vom· ing, myalgia, anorexia, thromb ope ia, OTA CASE or an hepatic transaminase elevation Probabl e Fourfold or greater rise 1in lgG Ab iter o Rickettsia typhi or R. felis an igen by IF CF, lA, MA, or IHA i ac e a d convalesce sera IFA, IA, MA, or IIHA ti er of specimens taken a least one w apart OR ~ 1:128 OR CF of?16 reacti e OT E etyphus a d po itive P R ssay to R. typhi or R. felis OR with R. typhi or R. fefis SFGR iters equal? demonstration o positi e R. typhi or R. felis IF of skin lesion (biopsy) or org n tissue ( utopsy) OR isol tion of R~ typhi or R. fefi cl inical specimen Are SFGR titers Are SFGR t i ers negatiVe or higher t han lower than phus titers? phus titers? IF =immunofluoresce ce antibody CF=compleme · fl ·io LA=la ex agglutina ·on Probable P obable SfGR A=micm gglutina io Fie bome OT ACAS E ofT phus =indirect haemaggluti ation ELC 2018 - Vectorborne Diseases Typhus 68 PCR=polymerase chai n rea io , Re , 09- 8 er NOT ACASE *Sp,otted Fever G oup R"ckettsia (SFGR) At least o e oHhe following: Class·f cat·on Allgor·thm1 rash, eschar, headac e, OTA CASE myalgia, a emia, rombocytopenia, or an hepa ic ransaminase elevation SFGR species include: R. aeschlimannii, R. afrtcoe, R. australis, R. conorii, R. Pro able heifongjiangensis, R. helve ·ca, R. honei, R. japonica, R. marmionii, R. massiliae, R. pork.er;, R. rickettsii, R. sibirica, R. sibirica mongolotimonae, and R. s/o aco. Species e eluded from his condition are: R. typhi, R. felis, and R~akari ourfold or greater rise in lgG antibody iter o Ric e io ricke sfi or at er SFGR a igen by IFA Serologic e ·dence of in ac e D convalesce t sera specimens OR If posir e b EU A/EIA, eleva ed (titer ~1:128) positi e P R to R. or o her SFG R req est Rickettsial panel ssay rickettsii lg o lgG antfbody Are phus a d SFGR ·ters spp. OR demonstration of SFG antige , in a ,estl g (EU is only a reactive wl h R. ricke sii or equal? biopsy/a opsyspecimen by IHC OR isol tion of screening est) o her SFGR an 1igen by I A R. rickettsii or other SFGR from a cl ini I specimen in cell culture as f lea-borne Are typhus ti ers nega ive or Are typh s titers higher typhus t est ing lower an SFG iters? than SFGR titers? Confirmed SFGR do e? IFAa lg tite.rs ore not reliable: false negatives and false positivesELC are 2018 common; - Vectorborne if only o low lgM titer,Diseases loo for alternate e planation for illness 69 Cannot rule out flea-bome phus ithout testing because antibod·es cross react Rev. 9--2018 Rickettsial Disease Case Investigation • Make sure ALL Rickettsial lab reports are in NEDSS • If only spotted fever testing done, see if sample can be forwarded to DSHS Rickettsial panel testing • Need to contact patient • Information about exposure to vectors • Travel history • Treatment information, including dates • Make sure all required fields are completed in NEDSS (refer to Data Entry Guidelines – Quick Reference section for patient demographics/lab report) ELC 2018 - Vectorborne Diseases 70 References • Centers for Disease Control and Prevention website: www.cdc.gov/rmsf/ • Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever, Ehrlichioses, and Anaplasmosis --- United States. A practical Guide for Physicians and Other Health-Care and Public Health Professionals: www.cdc.gov/mmwr/preview/mmwrhtml/rr5504a 1.htm • Byork, A. Trip Report: Assessment of human spotted fever in the Lower Rio Grande Valley of Texas (Epi-Aid 2010-101). ELC 2018 - Vectorborne Diseases 71 Arboviruses Testing options & interpretation • Test availability & requesting special testing for uncommon arboviruses • Blood donor screening for arboviruses (West Nile virus and Zika virus): how does it work? • Suspected false positive result at a commercial lab? What next? Texas Department of State Health Services • Scenarios ELC 2018 - Vectorborne Diseases 72 Arboviral Diagnostic Assays Specimen Test Type Availability Caveats Types Widespread - False positives and IgM antibody commercial and cross-reactivity Serum, CSF detection public health common, unclear labs duration of IgM Plaque Limited – public Time consuming, Reduction health labs only Serum, CSF cannot distinguish (certain states, Neutralization timing of infection Test (PRNT) CDC) Widespread - Serum, urine*, Limited window of commercial and CSF, whole PCR detection, false public health blood, amniotic positives possible labs fluid* Placenta, Very time Very limited – Tissue umbilical cord, consuming, cannot CDC only pathology products of distinguish between (requires pre- conception, fetal maternal and fetal (*Zika only) approval) losses infection ELC 2018 - Vectorborne Diseases 73 Plaque-Reduction Neutralization Test (PRNT) Texas Department of State Health Services • Requires mixing the patient’s serum with live virus to determine how effective it is at neutralizing the virus • Measures total neutralizing antibody rather than IgM specifically • Cross-reactivity issues with similar viruses Zika, dengue, WNV Source: http://www1.paho.org/hq/dmdocuments/2010/p4.lanciotti CHIK%20PAHO%20mtg%20Peru%202010_1_1.pdf ELC 2018 - Vectorborne Diseases 74 Tracking Testing Progress Commercial laboratory CDC laboratory Ordering (Fort Collins, provider Atlanta) Specimen DSHS Austin Lab reports laboratory ELC 2018 - Vectorborne Diseases 75 Uncommon Arboviral Diseases Texas Department of State Health Services • Tick -borne Encephalitis: endemic to parts of Europe • Japanese Encephalitis: endemic to Asia, vaccination available (diagnostic cross-reactivity with flaviviruses) • Yellow Fever: central Africa, South America (Brazil outbreak) at risk, vaccination available (diagnostic cross-reactivity with flaviviruses) • Powassan: rare, highest risk in Northeast US (flavivirus) • St. Louis Encephalitis: rare but endemic to Texas and US, cross-reactivity with West Nile as a flavivirus (panel test recommended) • Cache Valley: rare but some activity in North & Central America (Bunyamwera serogroup) • California serogroup, including California encephalitis, Jamestown Canyon, Keystone, La Crosse, Snowshoe hare, Keystone, and Trivittatus viruses: isolated cases • Eastern & Western Equine Encephalitis: rare, but picked up in animal surveillance in Texas • Heartland: emerging, <50 cases nationwide, likely spread by Lone Star Tick • Colorado Tick Fever: Dermacenter andersoni ticks (high elevation), uncommon ELC 2018 - Vectorborne Diseases 76 r bovirns Test ing Options and Locati ons (as of Sept ember 2018) CDC Fort CDC Dengu e Airbovirus DSHS Comme1rciial Lab Colllins1 Brancht Chikungunya PCR 2 Vess Yes Yes (last resort) Yes, Mayo Medica l lab, CP L4 , Focus Diaqnostics ( Quest), and ARUP IgM/ lgG Vess Yes Yes (last resort) Yes Mayo Medica l lab, CP L4 Focus Diaqnostics ( Quest) and ARUP PRNT No Yes Yes (last resort) No Denaue PCR 2 Vess No Yes Yes, Focus Diagnostics {Quest), ARUP NS1 No No Yes Yes, Mayo Medical Lab and Focus Diaqnostics (Quest) IgM/ lgG Vess Yes Yes (last resort) Yes CPL4 Viracor Focus Diaqnostics ( Quest), Mayo Medica l lab an d ARUP PRNT No Yes Yes (last resort) No Eastern/West ern Ectuine Encephalitis PCR No Yes No No IaM/ IaG No Yes No vess Mavo Medica l lab and most commercial labs PRNT No Yes No No Japanese Encephalitis PCR No Yes No No IaM/ IaG No Yes No Yes ARUP PRNT No Yes No No St. Louis Encephalitis PCR No Yes No No IaM/ IaG Vess Yes No vess, Mayo Med ical Lab and most commercial labs PRNT No Yes No No West Nile PCR No Yes No Vess ARUP CPL Mayo Medical La b, LabCorp, and Focus Diaqnostics (Quest) IaM/ IaG Vess Yes No Vess, ARUP, CPL, Mayo Medical Lab, LabCorp, and Focus Diaqnostics (Quest) PRNT No Yes No No Yellow Fever PCR No Yes No No IqM/ lqG No Yes No No PRNT No Yes No No Zika PCR 2 Vess Yes Yes (last resort) Yes ARUP CPL4 Focus Diaanostics (Quest). Mavo Medical lab, La bCoro Viracor and Bio Reference IaM 2/ laG Vess Yes Yes (last resort) Yes, ARUP, CPL4 , Focus Diaanostics (Quest), Mayo Medical lab, La bCor o, Viracor and Bio Refe rence PRNT No Yes Yes (last resort) No caliifornia seroqroup Cache Valley, Powassan, Tick-borne Encephalit is and other rare arboviruses Uncommon; Ca lifornia serogroup serology available through ARUP, Focus Diagnostics (Quest), and Mayo PCR, IgM, and/ or PRNT No Yes No Medica l lab 1 Sa mples that require CDC testing should be sent through DSHS after pnor coordmat1on with ZoonosIs Control. Please 1nd1cate which CDC test 1s being requested under section 9 ( CDC 1·eference test) on the G- 2A for m. 2 May also be performed at select LRl'Js, military bases and hospitals (contact y our local LRN, m ilitary base or hospital for infom1ation on which tests are being performed ). s Use G-2V fom1 req uest IgM or PCR for CHIK, ZIKA, DEN and/ or I gM for WNV and SLE; no IgG available. DSHS w il l forward to CDC, as needed. 4 CP L (9200 Wall St. ) is known by t he following aliases: Sonic reference lab and Sonic Healthcare USA. s Testing for SLE and Western/Eastern equine encephalit is includedELC in a 2018panel at -FoVectorbornecus Diagnost ics (Q Diseasesuest), Mayo Me dica l Lab, ARUP, and CP L ( includes West77 Nile plus previous arboviruses mentioned on their panel). DSHS Specimen Submission: G-2V Do not use sample Texas Department of State Health S•rvices forms from DSHS Lab website! Must contact the ...:.·""""'' L llat!Hl:etllOCll!!rol/!leH,JIDQ,amdgt,tt,~o.-~I\IS lo'd'lell!Sl..-d 'llli l'OINr1~~r,or...Oa,,;wtu~ttM•IAalbar•11e~d, l. i..&Gir.,g!l'l~:ICl:lf!Ol~farlO'Hl!~~-fHfll>a,~tltDMI ~f•~~lor~ors~-011115'9.bS'.',fttlrr~-. lab to create an account or =~ly-tffitl_aM_!N~-~IIHf .. !!i'~...!:'.':!':_:!!'!:::,~:~dM,,a,, "'tTfll,el; 9'9t',ll:K I. llpt.'a191-.N'll'IDIS IMkno.ttfi,.;aiNCl:illng~~-dts:Qnlllld request forms. □ ~utml~er;J,J Pr!Vitte ln5ur~\4J □ SIOS(li20) T8ElrrfNl!on(1tl8) □ BT0,..,,1 (1"••) TH•Xf>ll □ HIV I STD ('ISl)lf Ti!BXX(ll) □ ICIC.,,,:,1>t-•(1 l'XCL1'r1' (7J Zoonosis pa,Q) □ lmrnirut111Knl◄1~ , □ ... Zika, Dengue, and/or Chlkungunya Arbovlrus lgM (West NIie, Sl Louis Encephalitis) A Other. ______ tIDl5,; OSHS may test for Zlka, Dengue. Chlkungunya, West NIie (WN), SL Louis Encephalitis (SLE) and/or other emerging arbovlruses, as needed. Serology. PCR, or both wiN be performed at DSHS and the testing methodology and specific viruses analyzed will be based on dinical symptoms and current epldemlologlcal testing criteria. Testing may lnltlally be perlonned to Identify a specific suspected virus or viruses. Reftex testing may be ordered based on initial results andfor approval of additional testing. In some Instances. specimens may also be forwarded to CDC for furthBf testing. H!,l.!;.; OS~ ma~ ~to"llka, Dlmg~ . Cl'llktrgu~ W • i;!Nlto t. Loi.ii Er'nl!Nllii& (Sl.€) andlar Dlh~ mlef'i)frq~stis, Pat, orbcthw.11IN! c,ed,:trned IAOSHS and st r,,nu~l,At ~VI vvill~.-~ {lnllPCni..i rcal•ltll1o 11\T•Pc;I'\; m11 WUSC:s a1111 on dlnl::al Vac:me rtceiVM: □ ·•es D No S)'fflllims ani ~ epi;ScmioiGgjc: 11ering criuria. Tl:Slr'g rr.y IIVt.iiy FOR DSHS USE ONLY -. Ot,tc,.....eohett$COive<1: ______bto,-lbffi'IHlloid"""vs •f'Kllc.,~"'""'~vl--c. R•ll-1..uing mi~ bl oedanr,d basid on inti:11 IHJlls aMl'or ~ Id addi\l,n;:al ~ . TtN!fhi$131Y(lfknoW1'1): ------ltl.SO~ lrst.!!IC~ ~rre,smayMSO be fcrwadeoto :oc fo"fuf'lhtr □ Not Met Meastes, teaf..tlll& RT-PCR m"""' FOR DSHS USE ONL V - Date· Mu"l)S, rEal-tlrre RT-PCR r1t~ ? 0 Met C No1 IJICt MERS Coronavrus (~ovelcoronavirL&) oc cc tt.. PriOr~flotl,.o!Jhd.at..... OD CO CIII lllfecikut DIIM&e (51'2) 77'H67l1 lor Mw!Uti~ .~-~ ______o z______Ott---: ______O Oner: ~ AII0$1MW1M ...,.dlflfll\"'611Yn 11.. • • toml'ffllMla&fb!ct~jllClllll!ffiM,.IIOIJIIAlEOOfltmmllrMl llf.ct~PfQl'IDlh'>l)'.llJ i>taaanl: ••&t1N1pe,tffla111_,.fffl:IWdlnmflltmRIJIIE:F«IGMAfOAl'flhlllll:nD01 lr'lcllea'llnN'NWll fror,11: Plt,ilw-lMl'oml.. ~IOIOPJt~ •o,,,·~·... ,.h_. \"tirhM,...... dP"t:t!M11'?1!9!t' nu:,r.:u::1< CJ,.e-,... - .....- ~ Ufl-AlQtl, FOR I.ABORATORY USE O.~L Y Cold 78 DSHS Specimen Submission: G-2A G•2As,,.~...., .. ~tlO!l"-t'""•'1'l ,e,:ft401 Cl.IA #4S00ff06"" Health and Human Services Ulbi>ratOt'Y S.f"\11C\l!S 5-t!ctlon, MC•l'l-47 P. 0 . Box 149347, Al.l:.tln, TU~J; 79714·9347 ~; ll00W,W"Sln~""8t!n, Taas?t7S6 Texas Department of State (888 ) 963-7111 x7318 or (512> 776-7313 htt :/fwww.dshs.toJtH.gov/l•b Health S•rvices ED 1 ll•IIOl•-lin9-o-p..,...l""""n•.. i,;o,y1 nif.. • ~ "N~""lH~IIIO, ·~===o-r'-""="-'~~------ Texas Department of State Health,,. S•rvices ,,, • All LRNs have Trioplex PCR (Zika, Lubbock chikungunya, • and dengue) • Select LRNs have West Nile and/or Zika IgM capability consult with your LRN for ~• Corpus Christi confirmation on options ELC 2018 - Vectorborne Diseases 80 Blood Donor Screening • Blood collection agencies screen year- round for many infectious diseases using Nucleic Acid Amplification Tests (NAATs)* • West Nile: pooled donations • Zika: individual donations & pools • Reactive donors should be reported by blood collectors to [email protected] • West Nile: report as a Presumptive Viremic Donor (PVD) in NBS/ArboNet • Zika: further testing and/or investigation Texas Department of State Health Services needed before any reporting in NBS *NOT considered equivalent to diagnostic PCR assays in terms of case reporting ELC 2018 - Vectorborne Diseases 81 TEXAS DEPARTMENT OF STATE HEALTH SERVICES P.O. Box 149347 Ausiin, Tce,as 7871 4-9347 ~~) :.888-963-7111 ~~ JOHN HELLUSTEDT, M D, in': 1-800-735-2989 TEXAS ,COMMISSIONER www.dsh.s.statc.tx..us Health and Hum an Serv 1 ·ces March 6, 2018 Texas Department of 5t Two types of Zika Health S•rvices ate Dear Colleague, screening NAAT: The Texas Department of State Health Services {DSHS) Zoonosis Control Branch (ZCB) utilizes multiple forms ofstatewide surveillance to detect the presence of arboviruses, such as West Nile virus • Procleix – (WNV), and other zoonotic pathogens in Texas. The DSHS-ZCB relies on reports from blood collection .agencies to detect WNV, Zika virus (ZIKV), and Cha disease. under IND ; • I • I protocol, follow .. ' ' ' up PCR, IgM, Communicable disease reponing is requu un er . e exas ea and Safety Code Section 81.042 IgG required and Texas Administrative Code Section 97.2. To report, simply send a secure email to [email protected] or fax the report to 512-776-7454. Providing the following data points will • Cobas – FDA ~~ . approved, no CoUectlon Age-ncy; Unique BUI#; Test Name, Collection Date; Last Name, First Name, Donor Phone Number, Donor Address, Date of Birth, Age, Sex, Race, and Hispanic Ethnicity (YIN). longer IND If your location has a city or county health department, we recommend that you also share this same protocol infonnation with them. Contact information for the health department(s) serving the county where you are located can be found at www dshs texas goy/jdcu/investigationlconditjon:,'oontactsl. Thank you in advance for your partnership in this important public health activity. If you have questions. you may contact me at tom,sjdwa@dshs,texas,gov. Sinc.erely, Ba&I, 06 Oclul.Je1 2017 ~:'L~· Manager, Zoonosis Control Branch 82 ELC 2018 - Vectorborne Diseases Blood Donor Screening ZIKA PRNTExpectatio Lab Reports WNV ns Procleix Cobas NAAT NAAT Follow up Yes, repeats, No (only 2 No (only repeats testing by Trioplex PCR repeats of of initial test, blood collector (“alternative initial test) sometimes WNV expected? NAT”), Zika IgM and IgG) IgM & Zika IgG Public health No, unless Case-by- Yes, if symptoms testing concern of case, but develop post- needed? local unlikely donation transmission Report as a No No No (only as a confirmed or “not a case” probable case WNV PVD) with only initial reactive result? ELC 2018 - Vectorborne Diseases 83 Commercial Lab Issues False positive results • ARUP chikungunya IgM assay has been causing concern in recent months; CDC and ARUP working on a solution • IgM positive results in individuals who meet clinical criteria (at least fever) should be verified at DSHS • All commercial Zika IgM assays have specificity and sensitivity issues, and still require repeat and follow up testing at a public health lab (an automatic process!) • Interpret non-negative Zika IgMs with a grain of salt! Coordinate submission of suspected false- positive specimens to DSHS with your Regional Zoonosis Control office ELC 2018 - Vectorborne Diseases 84 Scenario #1 A physician contacts your office about a patient who recently returned one week ago from a trip to visit family in upstate New York, where they spent time outdoors and removed at least one tick from themselves. They are experiencing fever, headache, weakness, confusion, loss of coordination, and difficulty with speech. The provider wants to test CSF and serum for Powassan virus. What next? • Exposure and symptoms are plausible for Powassan • Consult Arbovirus Testing Options cheat-sheet • Testing available at CDC Fort Collins Texas Department of State • Contact Regional Zoonosis Control office about Health Services the patient’s background and to coordinate submission of specimens ELC 2018 - Vectorborne Diseases 85 Scenario #1, continued Which DSHS submission form should be filled out and how? Which tests do you want to request? • G-2A form, either using your public health submitter account or work with the patient’s provider to submit one Can recommend the physician pursue West Nile testing through commercial labs (or possible at DSHS) How should the specimen be shipped and the form be sent? Expected turnaround time for results? • Ensure the G -2A form is sent with the specimens, which should be shipped frozen to DSHS Austin. • At least 2 weeks, up to a month likely for IgM and PRNT; let physician know. ELC 2018 - Vectorborne Diseases 86 Scenario #2 Texas Department of State You see this result in NBS for a patient who lives in Health S•rvices Houston, with no other arbovirus testing. What next? Reporting Facility/Provider Date Collected Test Results Reporting Facility: 06/28/20 18 Chikungunya virus Ab.lgM: 1.49 IV ARUP LABORATORIES Reference Range: (<=0.79) - (FinaQ • You speak with the ordering provider and find out that the patient has not left their residence county in a month. • On 6/23/18, they felt feverish with chills and had a headache and myalgia after spending some evenings outside with family Should this result be reported as an arbovirus disease case yet? If yes, how? If no, what next? • With no exposure, does not make sense despite meeting lab and clinical criteria as probable chikungunya • Call ARUP to request the specimen be forwarded to DSHS Austin (ideally, frozen) ELC 2018 - Vectorborne Diseases 87 Scenario #2, continued Which DSHS submission form should be filled out and how? Which tests do you want to request? • G-2V form, either using your public health submitter account or work with the patient’s provider to submit one Zike. Dengue, and/or Chikungunya Can consider West Nile Albovirus lgM (W~s1 Nile, SI. Louis Encephatili-s) .l Olher. ______fever as well, but ~ DSHS may lesl for ZIiia. Oengu11t. Cbikungunya., w~ NUe (WN). St. Louis e:ne~11J[l)s (SLe I and/or olhet emf:,gi~ 3'boviMa$, ii$ nccd4id priority is to verify or Sero1o,gy. PCR, ar both will be performed at DSliS amt the tesllno melhoa'olo911 and 1peoflc >Anises analyzed will be based on clinical !>ymptoms and cunen4 eplctemloloe1lc11I te~tlng cnterla. Tesdng1m1.1y lnldall~ rule out the be perfo,med to i dentify a specific 1,uspected virur, or viruses. RefleK teYlng mav be onterad based on inltial ll!s:ults andJor approwl of adcfiUonaJ tE!Sling chikungunya result In some i:fl!i1ances, i;pecimens mav also be forwarded to CDC for fwther testjng_ Where to send the form? What information does Zoonosis Control need to have? • Let ZCB know the background info (and ideally a tracking shipment # for the specimen from ARUP) and send the form securely to ZCB; we will coordinate with DSHS lab ELC 2018 - Vectorborne Diseases 88 Scenario #2, continued Texas Department of State One week after the sample is shipped to DSHS, you see Health S•rvices this result in NBS for the patient. What next? Should you report this as an arbovirus disease case? Reporting Facility/Provider Reporting Facility: 06/28/2018 Chikungunya virus Ab.lgM: TX Austin.SPHL Negative Reporting Facility: 06128/2018 Chikungunya virus RNA: TXAustin.SPHL Not Detected Reporting Facility: 06128/2018 DENGUE VIRUS 1+2+3+4 RNA: TX Austin.SPHL Not Detected Reporting Facility: 06/28/2018 Zika virus RNA: TX Austin SPHL Nol Detected • The ARUP result has been ruled out as a false positive by the result from DSHS. Note Trioplex PCR ordered as it was a day 5 specimen. • Make comments in the ARUP lab to explain why it is “Not A Case”, or make a “Not A Case” chikungunya investigation and associate all labs ELC 2018 - Vectorborne Diseases 89 Questions? ELC 2018 - Vectorborne Diseases 90 Texas Department of State Health Services Thank you Kamesha Owens, MPH Bonny Mayes, MA Kelly Broussard, MPH Zoonosis Control Branch Epi Team ELC 2018 - Vectorborne Diseases 91